In addition to the protection provided by passively acquired immunoglobulins, the ingestion of colostrum provides the neonate with factors that protect mucosal surfaces from colonization by pathogens and from the uptake of antigens. The principal immunoglobulin in human external secretions, including colostrum and milk, is secretory IgA, with a preponderance of the IgA2 subclass. In some cases, it appears that colostral immune responses manifest selectively in the IgA1 or IgA2 subclass. However, the mechanisms which regulate the selective expression of isotype and subclass at mucosal surfaces are not clear. The purpose of this proposal is to examine the isotype and subclass distribution of colostral immune responses to orally-ingested antigens and to examine the immunoregulatory functions of cell populations and soluble factors in human colostrum. Colostrum will be examined for specific antibodies (free and in immune complexes) to orally-ingested antigens and to food antigens. Such antibodies will be studied to determine isotype and IgA subclass. In addition, attempts will be made to identify the source of previously identified regulatory factors in colostrum. Isolated cell types will be examined for the ability to produce factors with immunoregulatory activities. In some cases, somatic cell hybrids will be constructed between T cell fusion partners and colostral T cells to provide a continuous source of possible factors. To determine whether the failure to detect immunoglobulin-secreting plasma cells in human colostrum is due to factors within the mucosal environment, somatic cell hybrids will also be constructed between B cells from colostrum and B cell fusion partners. Finally, the possible involvement of isotype-specific binding factors (FCAlphaR and immunoglobulin binding factors) in the regulation of mucosal immune responses will be examined. Various cell types will be studied to determine the presence of membrane receptors for IgA (FcAlphaR). Such receptors will be examined for subclass specificity in the binding of IgA and for the release of factors with IgA binding activity.